A few years ago the applicant observed that either oral or parenteral administration of the common amino acid and food additive, monosodium glutamate (MSG), to infant animals induced hypothalamic lesions involving the rapid destruction of developing neurons. He has been examining such aspects of the phenomenon as regional, species and molecular specificity in an attempt to clarify its pathophysiology and determine what significance the neurotoxicity of this common amino acid might have for human health. In the process of investigating this brain damage syndrome, the applicant discovered that it can be reproduced by certain other amino acids which, like glutamate, are acidic amino acids. He also has found that the non-acidic amino acid, L-cysteine, produces brain lesions but not in the same regions or developing brain as are affected by acidic amino acids. The applicant is applying for renewal of grant support to enable him to continue studying these intriguing amino acid-induced neurotoxic phenomena. Methods and objectives will include: Ultrastructural analysis of brain tissue changes following exposure of fetal or neonatal animals (including primates) to sulphur amino acids (cysteine and homocysteine); use of radioactive cysteine (S35) to clarify the mechanism of cysteine-induced brain damage and see if it can be related to the mechanism of glutamate-induced brain damage; and microinjection of acidic amino acids into various regions of adult rat brain followed by ultrastructural analysis of the injection site to investigate possible differences in sensitivity of various neuronal groups to the toxic action of acidic amino acids.